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Abstract Coastal urbanization is a key driver of mangrove loss, yet its global impacts on mangroves have yet to be thoroughly understood. Here we present a fine-scale assessment of the hidden impacts of urbanization on mangroves mediated by climate, and the joint effects of urbanization and climate at the global scale. Surprisingly, both urbanization and climate had positive impacts on mangrove growth and carbon stock in some regions, which is different from the general belief of the adverse impacts from previous research. In total, 27.3% of global mangroves received positive impacts from urbanization regarding their extent and carbon stock, among which 59.5% are indirectly mediated by climate. Moreover, mangroves in subtropical/temperate climate zones experienced more indirect positive impacts from urbanization, which enhances local climate conditions for growth by altering temperature, rainfall and sea levels. These findings suggest the feasibility of facilitating mangrove conservation through effective urban planning to achieve coastal sustainability.

Abstract Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

This study investigated the clinical efficacy of Carbon dioxide (CO2) laser therapy combined with photodynamic therapy in male patients with condyloma acuminatum. A retrospective analysis was conducted on 120 male patients with genital warts treated at our hospital. Based on different treatment methods, they were divided into a control group and an observation group, each consisting of 60 cases. The control group received CO2laser treatment, while the observation group received photodynamic therapy and CO2 laser treatment. Levels of lymphocyte chemotactic factor (LTN), human beta-defensin-2 (HBD-2), B-cell lymphoma-2 (Bcl-2), interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), T lymphocytes (CD3+), inducible T cells (CD4+), suppressive T cells (CD8+), Male Sexual Function Index (MSFI) scores, Chinese version of the Genital Warts Quality of Life Scale (CECA10) scores, incidence of adverse reactions, recurrence rate, and total treatment effectiveness were compared between groups. After therapy, both groups showed reduced levels of Bcl-2 and TNF-α, but increased levels of IL-12. The observation group had significantly lower Bcl-2, TNF-α and greater IL-12 levels than the control group (p < 0.05). After therapy, both groups showed increased levels of CD3+ and CD4+ but lower levels of CD8+ than before treatment. The observation group had significantly greater CD3+ and CD4+ levels, but lower CD8+ levels than the control group (p < 0.05). The observation group had significantly higher CD3+ and CD4+ levels and lower CD8+ levels compared to the control group (p < 0.05). The incidence of complications in the observation group was significantly lower than in the control group (p < 0.05). CO2 laser therapy combined with 5-aminolevulinic acid photodynamic therapy demonstrates efficacy in treating male genital warts. This therapy can significantly reduce inflammation, improve immune function, and help improve quality-of-life.

The exploration of the first member of Permian Maokou Formation (Maokou 1) in the Weiyuan area of southern Sichuan Basin has been limited. Previous analyses of cast thin sections and argon ion electron microscopy based on earlier drilling data suggested that talc pores were the primary reservoir spaces, with talc formation significantly contributing to the reservoir. However, the latest drilling data shows substantial differences in the types of reservoir spaces and the genesis of the Maokou 1 marlstone reservoirs compared to earlier understanding. It is necessary to further clarify the main controlling factors for the development of these reservoirs in the Maokou 1 member. Through core observation, thin section identification, physical property analysis, nitrogen adsorption, argon ion polishing scanning electron microscopy, and quantitative pore characterization, the primary reservoir spaces and types of the Maokou 1 marlstone were analyzed from both qualitative and quantitative perspectives. The main controlling factors for the development of these reservoirs were identified by combining total organic carbon (TOC) content determination, rare earth element analysis, and whole rock X-ray diffraction. High-quality reservoirs in the Maokou 1 member of the Weiyuan area are developed in marlstone, characterized by low porosity and permeability fractures and pore-type reservoirs, predominantly Type Ⅲ with some Type Ⅱ reservoirs. The main reservoir spaces include corroded pores, organic matter pores, and talc pores and fractures, with pore development closely related to TOC content. Talc formation, dolomitization, and silicification did not significantly contribute to secondary reservoir spaces, and their contribution to porosity is minimal. The development of marlstone reservoirs is jointly controlled by early dissolution, sedimentary facies, and organic matter abundance. Early dissolution is the key to the formation of corroded pores and fractures, while high primary productivity and high organic matter settling rate of the inner gentle slope shallow water environment provided the material basis for the formation of organic matter pores. This understanding provides theoretical support for the exploration of similar oil and gas reservoirs in the basin.

Abstract Aim To provide an overview of the various influencing factors related to the positive aspects of caring for dementia patients by family caregivers. Design A systematic mixed studies review. Methods The Preferred Reporting Items for Systematic Reviews guided this protocol as reported. Peer-reviewed studies published in English from 1997 to the present will be searched via information sources, gray literature, and the following databases: Web of Science, PsycINFO, PubMed, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible trials will also be retrieved from ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. This will be a mixed studies review. The Mixed Method Appraisal Tool will be used for the mixed-method studies. The Newcastle–Ottawa Scale for case–control and cohort studies and the JBI quality scale for cross-sectional and interventional (i.e., randomized or quasi-experimental) studies will be consulted. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research will be used for the qualitative studies. All the data will be extricated with JBI data extraction tools. The convergent synthesis method will be used in the review. Discussion This systematic review will synthesize and analyze the factors that influence the positive aspects of caring for dementia patients by family caregivers. Conclusion The findings will help decision-makers to adopt more appropriate and effective interventions for caregivers of people with dementia. Patient or public contributions This review protocol will ascertain the factors affecting the mediation of and path to improved caregiving, explore the factors’ action mechanisms, and examine the controlling factors to design a more targeted intervention program to improve caregiving, thus improving dementia patients’ outcomes and care. Contributions of the findings will include evidence of strategies that address ongoing dementia caregiving issues and the identification of areas for future research.

Optical imaging in the second near-infrared (NIR-II; 900–1880 nm) window is currently a popular research topic in the field of biomedical imaging. This study aimed to explore the application value of NIR-II fluorescence imaging in foot and ankle surgeries. A lab-established NIR-II fluorescence surgical navigation system was developed and used to navigate foot and ankle surgeries which enabled obtaining more high-spatial-frequency information and a higher signal-to-background ratio (SBR) in NIR-II fluorescence images compared to NIR-I fluorescence images; our result demonstrates that NIR-II imaging could provide higher-contrast and larger-depth images to surgeons. Three types of clinical application scenarios (diabetic foot, calcaneal fracture, and lower extremity trauma) were included in this study. Using the NIR-II fluorescence imaging technique, we observed the ischemic region in the diabetic foot before morphological alterations, accurately determined the boundary of the ischemic region in the surgical incision, and fully assessed the blood supply condition of the flap. NIR-II fluorescence imaging can help surgeons precisely judge surgical margins, detect ischemic lesions early, and dynamically trace the perfusion process. We believe that portable and reliable NIR-II fluorescence imaging equipment and additional functional fluorescent probes can play crucial roles in precision surgery.

The Tibetan Plateau (TP) has undergone significant warming and humidification in recent years, resulting in rapid permafrost degradation and spatiotemporal variations in hydrological processes, such as subsurface water transport, hydrothermal conversion, and runoff generation. Understanding the mechanisms of hydrological processes in permafrost areas under changing climate is crucial for accurately evaluating hydrological responses on the TP. This study comprehensively discusses the permafrost hydrological processes of the TP under changing climate. Topics include climate conditions and permafrost states, subsurface water transport under freeze–thaw conditions, development of thermokarst lakes and hydrothermal processes, and runoff response during permafrost degradation. This study offers a comprehensive understanding of permafrost changes and their hydrological responses, contributing significantly to water security and sustainable development on the TP.

Abstract Objectives STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. Conclusions In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

Abstract Doxorubicin (DOX) is an important chemotherapeutic agent for the treatment of hematologic tumors and breast carcinoma. However, its clinical application is limited owing to severe cardiotoxicity. Pyroptosis is a form of programmed cell death linked to DOX-induced cardiotoxicity. Bone mesenchymal stem cell–derived exosomes (BMSC-Exos) and endothelial progenitor cells-derived exosomes (EPC-Exos) have a protective role in the myocardium. Here we found that BMSC-Exos could improve DOX-induced cardiotoxicity by inhibiting pyroptosis, but EPC-Exos couldn’t. Compared with EPCs-Exo, BMSC-Exo-overexpressing lncRNA GHET1 more effectively suppressed pyroptosis, protecting against DOX-induced cardiotoxicity. Further studies showed that lncRNA GHET1 effectively decreased the expression of Nod-like receptor protein 3 (NLRP3), which plays a vital role in pyroptosis by binding to IGF2 mRNA-binding protein 1 (IGF2BP1), a non-catalytic posttranscriptional enhancer of NLRP3 mRNA. In summary, lncRNA GHET1 released by BMSC-Exo ameliorated DOX-induced pyroptosis by targeting IGF2BP1 to reduce posttranscriptional stabilization of NLRP3.

Abstract The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

Abstract Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration. Graphical Abstract

Abstract The minimally invasive injection of tissue engineering scaffolds is of interest as it requires a smaller incision and quickens recovery. However, the engineering of scaffolds capable of injection remains a challenge. Here, we report on a shrunken scaffold inspired by the shrinking of puffed food in a humid environment. A scaffold is freeze-dried to remove water then placed in a humid atmosphere. The humidity causes the dry scaffold to shrink by up to 90%. In addition, the humidity treatment reduces the scaffolds modulus minimizing the foreign body response after implantation. The scaffolds can rapidly swell into their original size and shape after application. A tool for the delivery of the minimally invasive scaffolds is developed and we demonstrate the potential for minimally invasive delivery using this shrinking technique.

Abstract Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.

Abstract Objective Based on the Omaha problem classification system, a sensitivity outcome index system for home nursing of elderly liver transplant patients was established. Methods Through a comprehensive literature review and rigorous application of the Delphi method, a panel of 20 experts completed two rounds of effective letter consultation to obtain expert consensus opinions. The contents of indicators were determined based on this process, and the analytic hierarchy process was employed to confirm the weightage assigned to each indicator. Consequently, we established a sensitivity outcome index system for home care in elderly liver transplant patients. Results The effective recovery rate of the questionnaire in two rounds of expert consultation was 100%, and the proportion of experts who gave opinions was 55% and 15%, respectively, indicating that the experts were highly active. The expert authority coefficients were calculated as 0.904 and 0.905, respectively, indicating a high degree of expert authority. In the second round, Kendall’s coordination coefficients for primary, secondary, and tertiary indicators were determined to be 0.419, 0.418, and 0.394 (P

Abstract Objectives To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD). Methods From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression. Results Over a median follow-up time of 31.6 months (interquartile range: 12.9–49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515). Conclusion For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.

Abstract Background The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients. Methods This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C). Results Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P

Abstract Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions.

Abstract Background The role of diet choline in atherosclerotic cardiovascular disease (ASCVD) is uncertain. Findings from animal experiments are contradictory while there is a lack of clinical investigations. This study aimed to investigate the association between choline intake and ASCVD based on individuals from the National Health and Nutrition Examination Survey (NHANES) database. Methods This cross-sectional study was conducted in 5525 individuals from the NHANES between 2011 and 2018. Participants were categorized into the ASCVD (n = 5015) and non-ASCVD (n = 510) groups. Univariable and multivariable-adjusted regression analyses were employed to investigate the relationship between diet choline and pertinent covariates. Logistic regression analysis and restricted cubic spline analysis were used to evaluate the association between choline intake and ASCVD. Results ASCVD participants had higher choline intake compared to those without ASCVD. In the higher tertiles of choline intake, there was a greater proportion of males, married individuals, highly educated individuals, and those with increased physical activity, but a lower proportion of smokers and drinkers. In the higher tertiles of choline intake, a lower proportion of individuals had a history of congestive heart failure and stroke. After adjusting for age, gender, race, ethnicity, and physical activity, an inverse association between choline intake and heart disease, stroke, and ASCVD was found. A restricted cubic spline analysis showed a mirrored J-shaped relationship between choline and ASCVD, stroke and congestive heart failure in males. There was no association between dietary choline and metabolic syndrome. Conclusion An inverse association was observed between choline intake and ASVCD among U.S. adults. Further large longitudinal studies are needed to test the causal relationship of choline and ASVCD.

Abstract Background Drawing on the extensive utilization of traditional Chinese medicine (TCM) to combat COVID-19 in Mainland China, experts designed a series of TCM anti-epidemic strategies. This study aims to understand Hong Kong CM practitioners’ application of and opinions on the “Chinese Medicine Anti-epidemic Plans.” Methods Online focus group interviews were conducted, and purposive sampling was employed to invite 22 CM practitioners to voluntarily participate in three interview sessions. The interviews were audio recorded, then transcribed verbatim. The transcripts were analyzed using template analysis. Results Three themes were derived: (1) facilitators of the “Chinese Medicine Anti-epidemic Plans,” (2) barriers of the “Chinese Medicine Anti-epidemic Plans,” and (3) expectations on improving the “Chinese Medicine Anti-epidemic Plans.” The participants could obtain relevant information from various sources, which highlights the value of the plans for TCM medicinal cuisine and non-pharmacologic therapies and guiding junior CM practitioners, supplementing Western medicine interventions, and managing Chinese herb reserves in clinics. However, the barriers included the lack of a specialized platform for timely information release, defective plan content, limited reference value to experienced CM practitioners, and lack of applicability to Hong Kong. The expectations of the CM practitioners for improving the plans were identified based on the barriers. Conclusions To enhance the implementation of the anti-epidemic plans, CM practitioners in Hong Kong expect to utilize a specific CM platform and refine the plans to ensure that they are realistic, focused, comprehensive, and tailored to the local context.

Synectic Aperture Radar (SAR) backscatter coefficient is sensitive to glacier surface physical characteristic changes, including the states of melting and refreezing, but it is also sensitive to incidence angle variation. This study explores the capability of monitoring Greenland Ice Sheet (GrIS) melting status with Sentinel-1 dual-polarized images by referring to Automatic Weather Station (AWS) records. Sentinel-1 SAR images at five coastal regions of the GrIS are obtained from 2017 to 2021. The backscatter coefficients are normalized to an incidence angle of 30° with an empirical model. Time series of five backscatter coefficients profiles covering AWS illustrates different patterns of the ice surface dielectric constant dynamics in different elevations. The wet snow radar zone shows clear backscatter coefficients decreasing during the melting seasons, but the bare ice radar zone behaves more complexly during the melting seasons. The numbers of melting days at different elevations are also derived for each profile based on −3 dB backscatter coefficient decrease of HH and/or HV polarization, showing the heterogeneous ablation processes over the GrIS. The daily maximum 2 m air temperature on two consecutive days (before and on the SAR acquisition day) exceeds 0°C, and the daily average 2 m air temperature exceeds −0.5°C on the SAR acquisition day that was recorded by the AWS finds good agreements with the −3 dB decrease of the backscatter coefficients, suggesting the GrIS surface melting can be well captured by dual-polarized Sentinel-1 C-band SAR images. The overall agreement and Kappa coefficients are mostly better than 0.85 and 0.70, respectively, for HH images and 0.80 and 0.60, respectively, for HV images, suggesting a better performance of the co-polarized image. High temporal resolution and wide-swath SAR sequence imagery provide suitable data sources for monitoring glacier surface melting-refreezing stats; further analysis is requested to quantitatively link the volume of melting with backscatter coefficient and other SAR data sources.

The advantageous geographical location of the middle reaches of the Yangtze River (YRMR) plays an important role in promoting high-quality development in China and accelerating the development of the Yangtze River Economic Belt(YREB). In the new stage of development, green development efficiency (GDE) is an important metric for assessing the balance between economic development and ecological civilization. Therefore, taking three city clusters in China's YRMR as the study area, this research employs the Super-SBM model to assess their GDE in 2010–2020 in order to analyze the problem of GDE at the city scale. On this basis, spatio-temporal analyses, dynamic evolution, and convergence analyses have been carried out using the Thiel index, GML index model, and convergence model. The findings indicate that overall GDE has not yet reached an effective level and generally exhibits a two-stage fluctuating upward trend. Spatially, the pattern of distribution is ''high in the southwest, low in the northeast''. The differences within the city clusters in the YRMR in terms of green development are gradually narrowing, with differences within the same regions contributing the most to overall differences. The GML index shows a trend of fluctuating growth, indicating that the overall GDE growth is in good condition. GDE has grown significantly as a result of technological advancements, with the Wuhan metropolitan area (cluster A) experiencing the fastest growth in this regard, followed by the Chang-Zhu-Tan and the Poyang Lake rim city clusters (clusters B and C). The YRMR and its three major city clusters exhibit both σ- and β-convergence patterns. The convergence of GDE is simultaneously affected by several factors, including economic development (RGDP), urbanization level (UR), industrial structure (IND), technological development (TEC), and the level of openness (LO). Regional heterogeneity also exists. The above study provides decision-making references and empirical evidence for promoting green development in China's city clusters in the YRMR and advancing the improvement of economic-environmental incongruence in this area.

Heterotopic ossification (HO) is a pathological process that generates ectopic bone in soft tissues. Hedgehog signaling (Hh signaling) is a signaling pathway that plays an important role in embryonic development and involves three ligands: sonic hedgehog (Shh), Indian hedgehog (Ihh) and desert hedgehog (Dhh). Hh signaling also has an important role in skeletal development. This paper discusses the effects of Hh signaling on the process of HO formation and describes several signaling molecules that are involved in Hh-mediated processes: parathyroid Hormone-Related Protein (PTHrP) and Fkbp10 mediate the expression of Hh during chondrogenesic differentiation. Extracellular signal-regulated kinase (ERK), GNAs and Yes-Associated Protein (YAP) interact with Hh signaling to play a role in osteogenic differentiation. Runt-Related Transcription Factor 2 (Runx2), Mohawk gene (Mkx) and bone morphogenetic protein (BMP) mediate Hh signaling during both chondrogenic and osteogenic differentiation. This paper also discusses possible therapeutic options for HO, lists several Hh inhibitors and explores whether they could serve as emerging targets for the treatment of HO.

The release of carbon dioxide (CO2) from lakes is a critical element of carbon (C) emissions from inland waters. Within the realm of climate change, the inquiries surrounding whether lakes on the Tibetan Plateau (TP) function as C sources or sinks and the magnitude of CO2 exchange flux from these lakes have garnered significant attentions. Nevertheless, accurately assessing the lakes’ contribution to the C budgets poses challenges due to data scarcity and methodological inaccuracies. By amalgamating data from literature reviews and field measurements for different sizes of lakes during the ice-free (IF) and ice-covered (IC) periods from 2016 to 2021, this study offers a refined estimate of the CO2 exchange flux and flux rate for lakes on the TP by including lakes ranging in size from 0.01 to 1 km2 (small lakes) in the C budgets. Findings revealed that the annual CO2 exchange flux of TP lakes amounted to 7.10 Tg C yr–1, with 6.56 Tg C yr–1 and 0.54 Tg C yr–1 during the IF and IC periods, respectively. Notably, small lakes contributed 0.76 Tg C yr–1, representing 10.65 % of the total lake CO2 emissions on the TP, which indicates the significant role of small lakes in estimating CO2 emissions from TP lakes. The CO2 exchange fluxes of small lakes showed significant variability during the IF period, with the origins of lake water replenishment possibly explaining this diversity, where glacial meltwater replenishment is likely a key contributing factor. In contrast, CO2 emissions from small lakes increased during the IC period. The view of this study is that the groundwater recharge with higher CO2 concentrations and the shallow nature of small lakes may be the main reasons for the increase in CO2 emissions from small lakes during this period. The study underscores that the contribution of small lakes to the CO2 budgets of TP lakes is substantial and warrants attention, particularly in elucidating the mechanisms driving CO2 emissions from small lakes.

Objective Ophthalmic ward nursing work is onerous and busy, and many researchers have tried to introduce artificial intelligence (AI) technology to assist nurses in performing nursing tasks. This study aims to use augmented reality (AR) and AI technology to develop an intelligent assistant system for ophthalmic ward nurses and evaluate the usability and acceptability of the system in assisting clinical work for nurses. Methods Based on AR technology, under the framework of deep learning, the system management, functions, and interfaces were completed using acoustic recognition, voice interaction, and image recognition technologies. Finally, an intelligent assistance system with functions such as patient face recognition, automatic information matching, and nursing work management was developed. Ophthalmic day ward nurses were invited to participate in filling out the System Usability Scale (SUS). Using the AR-based intelligent assistance system (AR-IAS) as the experimental group and the existing personal digital assistant (PDA) system as the control group. The experimental results of the three subscales of learnability, efficiency, and satisfaction of the usability scale were compared, and the clinical usability score of the AR-IAS system was calculated. Results This study showed that the AR-IAS and the PDA systems had learnability subscale scores of 22.50/30.00 and 21.00/30.00, respectively; efficiency subscale scores of 29.67/40.00 and 28.67/40.00, respectively; and satisfaction subscale scores of 23.67/30.00 and 23.17/30.00, respectively. The overall usability score of the AR-IAS system was 75.83/100.00. Conclusion Based on the analysis results of the System Usability Scale, the AR-IAS system developed using AR and AI technology has good overall usability and can be accepted by clinical nurses. It is suitable for use in ophthalmic nursing tasks and has clinical promotion and further research value.

Background/Aims: Anti-programmed cell death protein 1 (PD-1) treatment has exhibited clinical benefits in colorectal cancer (CRC). However, the low response rate of CRC to immunotherapy is an urgent problem that needs to be solved. Materials and Methods: MC-38 tumor cells was challenged subcutaneously in the flank of 7-week-old male C57BL/6 mice. The mice were randomly divided into 3 groups, and 200µg/mouse anti-PD-1 antibody and 100 mg/kg RAS-Seletive Lethal 3 (RSL) or phosphate buffer saline (PBS) were intraperitoneally injected every 2 days. The expression of oxidative stress and ferroptosis-related genes was measured by Western blotting, real-time reverse transcription-polymerase chain reaction, Prussian blue staining, and enzyme-linked immunosorbent assay. Results: Anti-PD-1 treatment-unresponsive tumors showed stronger immunosuppression than responsive tumors. Notably, the responsive tumors showed higher levels of H2O2 and reactive oxygen species, both of which could impair the antitumor effect of cytotoxic CD8+ T cells. The anti-PD-1 treatment-responsive tumors showed a higher expression of pro-ferroptosis genes and Fe2+ accumulation than those of anti-PD-1 nonresponsive tumors, indicating the potential role of ferroptosis in the efficacy of anti-PD-1 treatment. In MC-38 syngeneic tumor model, (1S, 3R)‐RSL3 (RSL), a glutathione peroxidase 4 inhibitor, effectively promoted the antitumor effect of anti-PD-1 treatment in vivo. However, anti-PD-1 treatment did not affect the levels of ferroptosis-related genes in tumor model. Mechanistically, RSL treatment significantly upregulated the frequency of proliferating (ki67+) and cytotoxic (GZMB+) CD8+ T cells. Furthermore, the frequency of tumor neoantigen-specific interferon (IFN)-γ CD8+ T cells showed a significant increase after RSL plus anti-PD-1 treatment. Conclusion: RSL may be a promising drug for potentiating the antitumor efficiency of anti-PD-1 treatment in CRC.

Digital Elevation Model (DEM) errors tend to be spatially correlated, inevitably affecting DEM-based topographic change detection. Traditional topographic change detection methods often ignore the spatial distribution of the DEM error. This paper aims to develop a workflow that considers the spatial autocorrelation of the error in topographic change detection. Firstly, the DEM of Difference (DoD) is obtained from two-period DEMs, and the Monte Carlo method is employed to evaluate the Spatially Distributed Errors (SDE) in DEMs. Secondly, DoD errors are calculated by propagation based on spatially distributed DEM errors. At the same time, its spatial distribution is quantified using the semi-variance function. Finally, topographic changes (erosion, deposition, and net changes) are calculated based on the spatial distribution analysis and significance detection. The results in two small catchments indicate that DEM errors are spatially correlated, increasing the volume calculation errors. However, using Standard Deviation of Errors (SDE) instead of Root Mean Square Error (RMSE) can effectively reduce the sensitivity of the detection results in the significance threshold. When the significance threshold increases from 68% to 95%, the observations loss using the spatially distributed error is 4.67% −6.92% lower than that using the RMSE. The level of detection has little impact on the net topographic change and significantly influences gross erosion and deposition. In particular, the use of level of detection can effectively reduce the misclassification of erosion or deposition in stable topography areas. The proposed method can be effectively utilized in various applications like surface deformation monitoring, erosion monitoring, and sediment transport assessment.

Abstract Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification: traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD‐like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK). In the chondrogenesis stage, NF-κB signalling can promote chondrogenesis through interactions with mechanistic target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) and other molecules, including R-spondin 2 (Rspo2) and SRY-box 9 (Sox9). NF-κB expression can modulate osteoblast differentiation by upregulating secreted protein acidic and rich in cysteine (SPARC) and interacting with mTOR signalling, bone morphogenetic protein (BMP) signalling or integrin-mediated signalling under stretch stimulation in the final osteogenic stage. In FOP, mutated ACVR1-induced NF-κB signalling exacerbates inflammation in macrophages and can promote chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs) through interactions with smad signalling and mTOR signalling. This review summarizes the molecular mechanism of NF-κB signalling during HO and highlights potential therapeutics for treating HO.

Abstract Lower back pain (LBP), which is a primary cause of disability, is largely attributed to intervertebral disc degeneration (IDD). Macrophages (MΦs) in degenerated intervertebral discs (IVDs) form a chronic inflammatory microenvironment, but how MΦs are recruited to degenerative segments and transform into a proinflammatory phenotype remains unclear. We evaluated chemokine expression in degenerated nucleus pulposus cells (NPCs) to clarify the role of NPCs in the establishment of an inflammatory microenvironment in IDD and explored the mechanisms. We found that the production of C-C motif chemokine ligand 2 (CCL2) and C-C motif chemokine ligand 7 (CCL7) was significantly increased in NPCs under inflammatory conditions, and blocking CCL2/7 and their receptor, C-C chemokine receptor type 2(CCR2), inhibited the inductive effects of NPCs on MΦ infiltration and proinflammatory polarization. Moreover, activation of the integrated stress response (ISR) was obvious in IDD, and ISR inhibition reduced the production of CCL2/7 in NPCs. Further investigation revealed that activating Transcription Factor 3 (ATF3) responded to ISR activation, and ChIP-qPCR verified the DNA-binding activity of ATF3 on CCL2/7 promoters. In addition, we found that Toll-like receptor 4 (TLR4) inhibition modulated ISR activation, and TLR4 regulated the accumulation of mitochondrial reactive oxygen species (mtROS) and double-stranded RNA (dsRNA). Downregulating the level of mtROS reduced the amount of dsRNA and ISR activation. Deactivating the ISR or blocking CCL2/7 release alleviated inflammation and the progression of IDD in vivo. Moreover, MΦ infiltration and IDD were inhibited in CCR2-knockout mice. In conclusion, this study highlights the critical role of TLR4/mtROS/dsRNA axis-mediated ISR activation in the production of CCL2/7 and the progression of IDD, which provides promising therapeutic strategies for discogenic LBP.

Abstract Background Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. Methods PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. Results BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. Conclusion Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.

Abstract Background This study assessed the impact of pressure-controlled ventilation (PCV) focusing on end-inspiratory flow rate on the incidence of postoperative pulmonary complications (PPCs) and inflammation levels in patients undergoing spinal surgery in the prone position. Methods A total of 187 patients who underwent posterior spinal surgery were enrolled and randomly divided into 3 groups: 61 in the volume-controlled ventilation (VCV) group (group V), 62 in the PCV-volume-guaranteed (VG) group (group P1), and 64 in the PCV-VG end-expiratory zero flow rate group (group P2). Indicators including tidal volume (VT), peak airway pressure (Ppeak), and dynamic lung compliance (Cdyn) were recorded. The Ppeak, Cdyn, PETCO2, and oxygenation index (PaO2/FiO2) after intubation (T0), after prone position (T1), 60 min after prone position (T2), and after supine position at the end of surgery (T3) of the three groups were collected. Results In the within-group comparison, compared with T0, Ppeak increased at T1 − 2 in groups V and P1 (P

The continuous expansion and development of anthropogenic activities pose considerable threats to the habitats of myriad species. Therefore, exploring how to protect and optimize species’ habitats to achieve harmony between humans and nature is particularly important. As a paradise for wildlife, Poyang Lake is the habitat and breeding ground for birds, fish, and other aquatic organisms. In this study, adopting a multi-level perspective of ‘point-line-area’, we had an appliance for habitat conservation by constructing an ecological security pattern (ESP) in the Poyang Lake Ecoregion (PYLE). We produced land use and land cover from 2000 to 2040 using the random forest and cellular automata-Markov model. Combining morphological spatial pattern analysis, landscape pattern index, and Linkage Mapper, we constructed a long-term ESP in the PYLE considering habitat protection. The spatiotemporal dynamics of ESP were compared and analyzed. The results show that PYLE's rapid economic development led to extensive urban growth, encroaching on surrounding bare land, which could undermine local species’ survival. Based on PYLE's predicted ESP in 2040, we propose an optimized ‘one area, two zones, and multiple points’ scheme to prioritize habitat protection. This comprehensive study provides innovative ideas and novel insights for future research and policy formulation in habitat protection.

Background Type 3 cardiorenal syndrome (CRS type 3) triggers acute cardiac injury from acute kidney injury (AKI), raising mortality in AKI patients. We aimed to identify risk factors for CRS type 3 and develop a predictive nomogram.Methods In this retrospective study, 805 AKI patients admitted at the Department of Nephrology, Second Hospital of Shanxi Medical University from 1 January 2017, to 31 December 2021, were categorized into a study cohort (406 patients from 2017.1.1-2021.6.30, with 63 CRS type 3 cases) and a validation cohort (126 patients from 1 July 2021 to 31 Dec 2021, with 22 CRS type 3 cases). Risk factors for CRS type 3, identified by logistic regression, informed the construction of a predictive nomogram. Its performance and accuracy were evaluated by the area under the curve (AUC), calibration curve and decision curve analysis, with further validation through a validation cohort.Results The nomogram included 6 risk factors: age (OR = 1.03; 95%CI = 1.009–1.052; p = 0.006), cardiovascular disease (CVD) history (OR = 2.802; 95%CI = 1.193–6.582; p = 0.018), mean artery pressure (MAP) (OR = 1.033; 95%CI = 1.012–1.054; p = 0.002), hemoglobin (OR = 0.973; 95%CI = 0.96-–0.987; p

ABSTRACTDiet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

Irradiation-induced defects such as dislocation loops, cavities or solute clusters and chemical composition segregation of reactor pressure vessel (RPV) steel are the root causes of irradiation embrittlement. Combining two nucleation mechanisms, namely, the uniform nucleation and non-uniform nucleation of solute clusters (such as Cu-rich phase), a cluster kinetic simulation was established based on the reaction rate theory, and the co-evolution of matrix damage and Cu-rich phase in low-copper RPV steel was simulated under irradiation. And the average size and number density of defective clusters and solute clusters were established with irradiation dose. Compared with the average size and number density of dislocation loops observed by transmission electron microscopy (TEM) of proton irradiated RPV steel at 290°C, the verification results show that the cluster dynamics model considering both the nucleation mechanism of interstitial dislocation loops and vacancy clusters can well simulate the irradiation damage behavior of materials.

BackgroundThe equity of public resources triggered by city shrinkage is a global challenge. Significantly, the impact of city shrinkage on the allocation of health service resources needs to be better understood. This study explores the impact of population change on government investment and health service delivery in shrinking cities.Data and methodUsing data from China’s Urban Statistical Yearbook (2010–2020), we employ regression discontinuity (RD) and fixed-effect models to examine the causal relationship between city shrinkage and health service provision.ResultShrinking cities show significant disparities in health resources, particularly in bed numbers (−1,167.58, p

Permafrost degradation on the Tibetan Plateau (TP) is anticipated to result in the thaw of permafrost carbon. Existing studies have been conducted to assess the future thaw of frozen carbon on the TP, primarily focusing on the deepening of the active layer while neglecting the impact of permafrost area shrinkage. This oversight may lead to a significant underestimation of the potential thaw of frozen carbon. Our research underscores the pivotal role of permafrost area shrinkage in estimating the future thaw of frozen carbon. Our findings reveal that when the combined effects of permafrost area shrinkage and active layer deepening are considered, the thaw rates of frozen carbon in various radiative forcing scenarios are nearly four times those based on active layer deepening alone. Notably, our results demonstrate substantial thaw of frozen organic carbon in the TP permafrost area under all four future scenarios: In the low radiative forcing scenario SSP1-2.6, it is predicted that 55.4 % of the organic carbon in the permafrost area 0–10 m soils will be in a state of thaw by 2100, and more than 90 % in the high radiative forcing scenario SSP5-8.5. This substantial thaw is poised to diminish the TP's current carbon sink function significantly. Our study emphasizes that as global warming persists, frozen carbon in permafrost areas will play a more active role in global carbon cycle processes in the future. Furthermore, we stress the importance of considering permafrost area shrinkage in understanding the thaw of frozen carbon, providing valuable insights for carbon balance studies on the TP.

Food waste (FW) from large dining facility has been a pressing environmental challenge in China recently. This study developed an innovative species-specific feeding strategy for producing pigeon meat and excellent manure from FW. Adding FW to the feed of pigeons significantly increased their feed intake and promoted their growth although the pigeons showed a strong aversion to the FW. We produced a “super manure” with exceptionally high nitrogen (N) content (mean = 10.77 % on a dry basis, 8.04–12.57 %, n = 264) by feeding slowly-growing pigeon species (Columba livia vs. and Caoge Huzhou 11) with protein-high commercial feed and FW. A significant negative relationship between the N and carbon (C) contents in the pigeon manure was found, with C depletion higher than N depletion. Furthermore, the N content in the anaerobic composting (AnC) manure was 29.16 % higher than that in the FW. Fourier transform infrared (FT-IR) analysis and stable isotopes δ13C and δ15N in the manure clearly identified the transformations of nutrients during pigeon feeding and the AnC process. This study opens a path for producing N-high manure using protein-high food waste.

Abstract Biochar application is widely recognized as an effective approach for increasing soil organic carbon (SOC) and mitigating climate change in agroecosystems. However, the effects of biochar application on net accumulations and relative contributions of different SOC sources remain unclear. Here, we explored the effects of biochar application on plant‐derived (PDC) and microbial necromass C (MNC) in a 10‐year experimental rice–wheat rotation field receiving four different intensities of biochar application (0, 2.25, 11.5, and 22.5 t ha−1 for each crop season), using phospholipid fatty acids (PLFAs), lignin phenols and amino sugars as biomarkers of microbial biomass, PDC and MNC, respectively. Our results showed that biochar application increased SOC content and stock by 32.6%–203% and 26.4%–145%, respectively. Higher biochar application (11.5 and 22.5 t ha−1) increased soil pH, total nitrogen (TN), total phosphorus (TP), SOC/TN, and root biomass. In addition, higher biochar application enhanced bacterial, fungal, and total microbial biomass. Plant lignin phenols and MNC contents significantly increased, whereas their contributions to SOC significantly decreased with the increase in biochar application rates due to the disproportionate increase in PDC and MNC, and SOC. Fungal necromass had a greater contribution to SOC than bacterial necromass. The fungal/bacterial necromass decreased from 2.56 to 2.26 with increasing biochar application rates, because of the higher abundances of bacteria than that of fungi as indicated by PLFAs under higher biochar application rates. Random forest analyses revealed that pH, TP, and SOC/TN were the main factors controlling plant lignin and MNC accumulation. Structural equation modeling revealed that biochar application increased lignin phenols by stimulating root biomass, whereas enhanced MNC accumulation was primarily from increased microbial biomass and lignin phenols. Overall, our findings suggest that biochar application increases the accumulation of the two SOC sources but decreases their contributions to SOC in paddy soils.

Safety is a top concern for the civil aviation industry, and the risk of safety accidents will increase due to pilot fatigue. To ensure the safety of civil aviation, this paper proposes a method to solve the crew scheduling problem considering pilot fatigue. In order to reflect individual differences and fatigue levels of pilots, an improved three-stage alertness calculation model is first proposed based on subjective and objective perspectives to represent pilots’ alertness levels and fatigue working duration quantitatively. Then, for the crew scheduling problem considering pilot fatigue, a mixed integer programming model is constructed to simultaneously achieve the optimization objectives of reducing the overall scheduling cost and crew fatigue working duration. Next, since the actual crew scheduling problem is large-scale, a solution algorithm based on a column generation framework is developed to improve the quality and efficiency of solving the large-scale crew scheduling problem. Furthermore, in the case study, we collected actual data from an airline company to validate the effectiveness of our proposed method. Finally, through multiple experimental comparisons and analyses, to balance the two optimization objectives mentioned above, it is more reasonable to handle pilot fatigue working duration with soft constraints. Sensitivity analysis reveals the variation rules of the crew cost and fatigue, providing some valuable managerial insights for the crew scheduling problem considering pilot fatigue.

Abstract Background Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. Methods IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. Results Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. Conclusion The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

Abstract Background Intervertebral disc degeneration (IVDD) is the major cause of low-back pain. Histone deacetylase 9 (HDAC9) was dramatically decreased in the degenerative nucleus pulposus (NP) samples of patients with intervertebral disc degeneration (IVDD) according to bioinformatics analysis of Gene Expression Omnibus (GEO) GSE56081 dataset. This study aims to investigate the role of HDAC9 in IVDD progression. Methods The contribution of HDAC9 to the progression of IVDD was assessed using HDAC9 knockout (HDAC9KO) mice and NP-targeted HDAC9-overexpressing mice by IVD injection of adenovirus-mediated HDAC9 under a Col2a1 promoter. Magnetic resonance imaging (MRI) and histological analysis were used to examine the degeneration of IVD. NP cells were isolated from mice to investigate the effects of HDAC9 on apoptosis and viability. mRNA-seq and coimmunoprecipitation/mass spectrometry (co-IP/MS) analysis were used to analyze the HDAC9-regulated factors in the primary cultured NP cells. Results HDAC9 was statistically decreased in the NP tissues in aged mice. HDAC9KO mice spontaneously developed age-related IVDD compared with wild-type (HDAC9WT) mice. In addition, overexpression of HDAC9 in NP cells alleviated IVDD symptoms in a surgically-induced IVDD mouse model. In an in vitro assay, knockdown of HDAC9 inhibited cell viability and promoted cell apoptosis of NP cells, and HDAC9 overexpression had the opposite effects in NP cells isolated from HDAC9KO mice. Results of mRNA-seq and co-IP/MS analysis revealed the possible proteins and signaling pathways regulated by HDAC9 in NP cells. RUNX family transcription factor 3 (RUNX3) was screened out for further study, and RUNX3 was found to be deacetylated and stabilized by HDAC9. Knockdown of RUNX3 restored the effects of HDAC9 silencing on NP cells by inhibiting apoptosis and increasing viability. Conclusion Our results suggest that HDAC9 plays an important role in the development and progression of IVDD. It might be required to protect NP cells against the loss of cell viability and apoptosis by inhibiting RUNX3 acetylation and expression during IVDD. Together, our findings suggest that HDAC9 may be a potential therapeutic target in IVDD. Graphical Abstract

Abstract To explore the influence of wind speed on the quality of tobacco in this study, we employed a heat pump-powered intensive curing barn and a three-stage curing process. By evaluating the influence of fan parameters on the quality of tobacco leaves at different curing stages, the optimal wind speed was determined. After adopting the optimized wind speed process, the degradation of macromolecular substances was faster, the accumulation of aroma substances was delayed to 55 °C, and the accumulation was more complete. Among them, the contents of reducing sugar and total sugar in flue-cured tobacco leaves were 22.25% and 29.2%, respectively, which were lower than those in the control group. The sugar was converted into more aroma substances, and the total amount of neutral aroma substances was 48.82% higher than that of the control group. The content of related aroma substances increased significantly. The content of petroleum ether extract related to aroma substances increased by 0.93% compared with the control group. The macromolecular substances were degraded more fully than the control group, such as the starch content decreased to 1.56%. The results of metabolomics showed that the contents of aldehydes, heterocyclic compounds, alcohols, ketones and esters increased significantly in different degrees after this process. These results show that the optimization of wind speed parameters can significantly improve the baking quality of tobacco leaves. This study provides a reference for the optimization of the flue-cured tobacco baking process.

Land subsidence, a common geological phenomenon in deltaic regions, poses significant risks to infrastructures, environments, and human lives. Monitoring and understanding land subsidence are crucial for establishing resilient, adaptive, and sustainable environments. In this study, a robust multi-temporal interferometric synthetic aperture radar (MTInSAR) method was employed to monitor land subsidence in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) using 541 Sentinel-1 SAR images. Spatial auto- and cross-correlation analysis were applied to select the most reasonable explanatory variables from nine candidates in each city of the GBA. City-level geographically weighted regression (GWR) models were then constructed to explore the spatially nonstationary effects of natural and human-induced factors. The findings revealed subsidence velocities ranging from 0 to 83.7 mm/yr in the GBA from 2015 to 2021, with the dominant factors affecting subsidence varying among regions. Natural and human-related factors accounted for 51.13% and 48.87%, respectively. Further analysis of representative subsidence areas highlights the importance of continuous monitoring of ground deformation using MTInSAR, region-specific land subsidence mitigation strategies, and regular maintenance of urban infrastructure. These insights are valuable for policymakers and urban planners in comprehending the complex processes underlying land subsidence and informing decision-making processes for sustainable and resilient urban development.

A novel approach is introduced for the detection of the location and direction of traffic congestion using GPS data from taxis. This approach uses a dynamic model that conceptualizes events, processes, and states. The states are the locations of the taxis, the processes are the motion of taxis, and the events are congestion. The model is implemented as a graph database, which represents the relationships between states, events, processes, and things (such as points of interest and road grid). Algorithms for constructing and updating the relationships and taxi behaviors dynamic retrieval method in Neo4j are presented and are used to demonstrate the capabilities in dynamic expression and reasoning. An implementation of Shanghai in 2015 finally demonstrated the ability of congestion direction detection and the cause searching of traffic congestion.

Rich observation data generated by ubiquitous sensors are vital for wetland monitoring, spanning from the prediction of natural disasters to emergency response. Such sensors use different data acquisition and description methods and, if combined, could provide a comprehensive description of the wetland. Unfortunately, these data remain hidden in isolated silos, and their variety makes integration and interoperability a significant challenge. In this work, we develop a semantic model for wetland monitoring data using an agile and modular approach, namely, wetland monitoring ontology (WMO), which contains five modules: wetland ecosystem, monitoring indicator, monitoring context, geospatial context, and temporal context. The proposed ontology supports the semantic interoperability and integration of wetland monitoring data from multiple sources, domains, modes, and spatiotemporal scales. We also provide two real-world use cases to validate the WMO and demonstrate the WMO’s usability and reusability.

Abstract The phenomenon of water aeration is serious after the overflow weir in the siphon well at the cooling water circulation system of coastal power plants. At present, designing special hydraulic structures is an effective way to reduce the intensity of aeration. In this paper, three engineering structure schemes were designed, and the three‐dimensional Realizable k–ε turbulence model was used. The volume of fluid method was introduced to capture the free water surface, and the unstructured grid was used to construct the two‐phase turbulent flow field. The aeration concentration and pressure distribution, obtained by numerical simulation, were basically consistent with the physical model test results. The results showed that the flow field at the orifice plates of cases 1 and 2 changed drastically, and the turbulent kinetic energy downstream of the orifice plate decreased with the increase of the number of holes. As for case 3, it showed that the high‐speed water flow fell into the water cushion pool, tumbling and sucking up a lot of air, and the turbulent kinetic energy and Reynolds stress were significantly greater than the other two cases. The hydraulic structure changed the cavitation characteristics of the downflow water, and the sequence of aeration concentration of the horizontal section was case 3 > case 1 > case 2. The aeration concentration was only 9.18%–17.86% in case 2. The aeration concentration at stable time is expressed as a function of the relative water depth y/y90 and the turbulent diffusion coefficient D. The distribution formula of aeration concentration was established, and its validity was verified by literatures. The results of this study will provide a certain reference for in‐depth analysis of water–air mixing motion characteristics, and simultaneously, it will have a guiding significance for the design of siphon well defoaming engineering.

Abstract Breast cancer is the most prevalent cancer globally, endangering women’s physical and mental health. Phospholipase D3 (PLD3) belongs to the phosphodiesterase family (PLD). PLD3 is related to insulin-mediated phosphorylation of the AKT pathway, suggesting that it may play a role in the occurrence and development of malignant tumors. This study may further explore the molecular mechanism of PLD3 inhibiting breast cancer cell proliferation. In this study, we demonstrated that PLD3 and miR-6796 are co-expressed in breast cancer. PLD3 can bind with CDK1 and inhibit its expression, leading to mitotic arrest and inhibiting breast cancer proliferation. Wild-type p53 regulates PLD3 and miR-6796 expression by competitively binding to the PLD3 promoter with ZEB1. DNMT3B, as the target gene of miR-6796, is recruited into the PLD3 promoter by combining with ZEB1 to regulate the DNA methylation of the PLD3 promoter and ultimately affect PLD3 and miR-6796 expression. In conclusion, we revealed the role and molecular mechanism of PLD3 and its embedded miR-6796 in breast cancer proliferation, providing clues and a theoretical foundation for future research and development of therapeutic targets and prognostic markers for breast cancer.

The Internet of Things (IoT) technology connects the real and network worlds by integrating sensors and internet technology, which has greatly changed people’s lifestyles, showing its broad application prospects. However, traditional materials for the sensors and power components used in the IoT limit its development for high-precision detection, long-term endurance, and multi-scenario applications. Metal halide perovskite, with unique advantages such as excellent photoelectric properties, an adjustable bandgap, flexibility, and a mild process, exhibits enormous potential to meet the requirements for IoT development. This paper provides a comprehensive review of metal halide perovskite’s application in sensors and energy supply modules within IoT systems. Advances in perovskite-based sensors, such as for gas, humidity, photoelectric, and optical sensors, are discussed. The application of indoor photovoltaics based on perovskite in IoT systems is also discussed. Lastly, the application prospects and challenges of perovskite-based devices in the IoT are summarized.

Non-invasive/minimally invasive continuous monitoring of blood glucose and blood glucose administration have a high impact on chronic disease management in diabetic patients, but the existing technology is yet to achieve the above two purposes at the same time. Therefore, this study proposes a microfluidic microneedle patch based on 3D printing technology and an integrated control system design for blood glucose measurement, and a drug delivery control circuit based on a 555 chip. The proposed method provides an improved preparation of a PVA-PEG-MoS2 nanosheet hydrogel, making use of its dielectric properties to fabricate a microcapacitor and then embedding it in a microfluidic chip. When MoS2 nanosheets react with interstitial liquid glucose (and during the calibration process), the permittivity of the hydrogel is changed, resulting in changes in the capacitance of the capacitor. By converting the capacitance change into the square-wave period change in the output of the 555 chip with the control circuit design accordingly, the minimally invasive continuous measurement of blood glucose and the controlled release of hypoglycemic drugs are realized. In this study, the cross-linking structure of MoS2 nanosheets in hydrogel was examined using infrared spectroscopy and scanning electron microscopy (SEM) methods. Moreover, the critical doping mass fraction of MoS2 nanosheets was determined to be 2% via the measurement of the dielectric constant. Meanwhile, the circuit design and the relationship between the pulse cycle and glucose concentration is validated. The results show that, compared with capacitors in series, the microcapacitors embedded in microfluidic channels can be connected in parallel to obtain better linearized blood glucose measurement results.